Posttransplant primary cutaneous Ki-1 (CD30)+/CD56+ anaplastic large cell lymphoma

An anaplastic large cell lymphoma that was negative for Epstein-Barr virus and positive for Ki-1 (CD30) presented as a polypoid scalp mass in a 56-year-old man 16 years after renal transplantation. The lymphoma was of the CD4+ cytotoxic T-cell lineage, and the tumor cells also expressed CD56. Despite reduction in the dose of immunosuppression and localized radiotherapy, the tumor had rapidly progressed to involve the soft tissue of the right hand. Systemic chemotherapy induced complete regression of the soft tissue lesion. This case illustrates that posttransplant primary cutaneous CD30+ anaplastic large cell lymphomas may assume an aggressive clinical course but can still be controlled by systemic chemotherapy.     

皮肤原发性CD30阳性间变性大细胞淋巴瘤

目的 探讨皮肤原发性CD30阳性间变性大细胞淋巴瘤（ALCL）的临床及组织病理学特征,为病理诊断和鉴别诊断提供依据。方法 采用组织病理学及免疫组织化学SP法的白细胞共同抗原、CD20、CD30、CD45RO、CD68、上皮膜抗原、细胞角蛋白和HMB45染色对9例皮肤原发性CD30阳性ALCL进行观察。结果 患者年龄31-84岁（平均58.2岁）,男女之比2：1,均以皮肤丘疹或皮下包块就诊。组织形态;瘤细胞体积大,呈多形性、圆形或椭圆形,胞质丰富。核大,核仁明显,核分型象多,常见R-S样细胞和多核巨细胞,CD30阳性,其中6例同时表达CD45RO,非T非B型3例表达,随访：2例因肿瘤转移而死亡,2例肿瘤复发,5例无复发,健在。结论 皮肤原发性CD30阳性ALCL是具有独特形态特点及预后较好的肿瘤,根组织病理特征及CD30阳性,可与其他恶性肿瘤鉴别。     

Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma

Primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL) represents a distinct clinical subtype of CD30+ anaplastic large cell lymphomas. The etiology and underlying molecular pathogenesis of C-ALCL remain unclear. This study aimed to investigate genetic changes in C-ALCL. Comparative genomic hybridization (CGH) analysis of 23 DNA samples from 15 C-ALCL cases identified chromosome imbalances (CI) in 10 samples from eight cases (43%). The mean number of CI per sample was 2.09 +/- 3.86, with gains (2.00 +/- 3.85) more common than losses (0.09 +/- 0.29). The most frequent CI were gains of 1/1p and 5 (50%) and 6, 7, 8/8p, and 19 (38%). Microarray-based CGH analysis of six DNA samples from five cases with CI revealed genomic imbalances (GI) in all of the cases studied. This included oncogene copy number gains of FGFR1 (8p11) in three cases, and NRAS (1p13.2), MYCN (2p24.1), RAF1 (3p25), CTSB (8p22), FES (15q26.1), and CBFA2 (21q22.3) in two cases. Real-time PCR analysis of nine DNA samples from eight cases with CI and GI detected amplifications of CTSB and RAF1 in seven cases (88%), REL (2p13p12) and JUNB (19p13.2) in six cases (75%), and MYCN and YES1 (18p11.3) in four cases (50%). Immunohistochemical staining of paraffin sections from six cases demonstrated expression of JUNB protein in five cases and BCL2 in three cases. These results reveal a consistent pattern of genetic alterations in C-ALCL and provide the molecular basis for further investigation of this disease.     

Posttransplant CD30+ (Ki-1) anaplastic large cell lymphoma: a case report and review of the literature

Posttransplant CD30(+) (Ki-1) anaplastic large cell lymphoma (ALCL) is rare. A review of the literature revealed only 3 such cases. All 3 cases were developed after single-organ transplantation. We describe CD30(+) (Ki-1) ALCL in a dual-organ (liver and heart) transplantation recipient. The patient was a 68-year-old white female who underwent an orthotopic heart transplantation in 1999 and a liver transplantation in 2000. She presented with nausea and was found to have CD30(+) (Ki-1) ALCL by pathologic examination of the gastric antrum biopsy specimen. To our knowledge, this patient represents the first reported case of posttransplant CD30(+) ALCL following a dual-organ transplantation.     

The ultrastructural and immunohistochemical heterogeneity of CD-30-positive neoplasms: so-called anaplastic large cell Ki-1 lymphomas

Anaplastic large cell lymphoma (ALCL), also referred to as Ki-1 lymphomas, was first recognized as an entity with characteristic light microscopic appearance in 1985. This tumor is composed of variably cohesive cells, often with large, markedly atypical, and multinucleated cellular forms. The recognition of ALCL resulted from the development of a monoclonal antibody in Kiel, Germany, named Ki-1, which was initially believed to be a putative marker for Reed-Sternberg cells. This antibody was later found to be specific against the epitope CD-30. Attempts to create strict criteria to preserve this neoplasm as a specific entity have undergone evolution. However, it is now clear that included in this group are a variety of pleomorphic neoplasms with CD-30 immunoreactivity. Some of these neoplasms are nonlymphoid and show marked heterogeneity in their immunohistochemical and ultrastructural profiles. This article aims to highlight the ultrastructural spectrum of neoplasms exhibiting CD-30 positivity that are within the spectrum of ALCL. It remains to be determined if there are subgroups of these CD-30-positive neoplasms that can be segregated on the basis of ultrastructural and immunohistochemical criteria with corresponding clinical correlates that may impact on their management, treatment, and prognosis. We review here the heterogeneity of CD-30-positive neoplasms (so-called anaplastic large cell Ki-1 lymphomas).     

Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1 + with a high content of reactive histiocytes)

We describe 13 cases of a peculiar lymphoid tumour containing very large numbers of reactive histiocytes. The tumours occurred in young patients (mean age 14.8 y) who presented with systemic symptoms and superficial lymphadenopathy. Microscopic examination revealed a diffuse effacement of lymph node structure due to the presence of histiocytes intermingled with a variable number of anaplastic large lymphoid cells. The latter, in some cases, were isolated, while in others they were arranged in clusters or were diffusely present in residual sinuses. The large anaplastic cells expressed the activation markers CD30 (Ki-1), CD25 (interleukin-2 receptor), CD70 (Ki-24) and Ki-27, as well as varying combinations of T-associated molecules. The histiocytes expressed lysozyme and the CD11b (C3bi-R), CD11c (p150, 95) CD14, CD68 (KPI) and Ber-Mac3 antigens. Double staining with the antibody Ki-67 demonstrated that the proliferating components were the CD30-positive cells and not the histiocytes. T-cell receptor beta gene rearrangements were shown in three cases tested. The patients responded well to aggressive chemotherapy and nine are still alive, eight in complete remission. It is suggested that the tumour represents a well-defined clinico-pathological entity originating from activated T-lymphocytes.     

Primary cutaneous CD30+ large cell B-cell lymphoma: a series of 10 cases.

BACKGROUND: White CD30 expression is described in extracutaneous diffuse large B-cell lymphomas, a primary cutaneous B-cell lymphoma (PCBCL) equivalent is not well defined. METHODS: Between June 1999 and July 2002 the authors encountered 10 patients with CD30+ PCBCLs of the large cell type. RESULTS: The patients comprised seven women and three men; five patients were over 80 years of age, all except one presenting with solitary plaques. With the exception of one death from myocardial infarction and one recurrence, all patients are well at a mean follow-up of 23.4 months. Skin biopsies showed a background of T-cell-rich reactive lymphoid hyperplasia in 7 of 10 patients, with variable granulomatous inflammation in 5 cases. The neoplastic large cells were immunoblastic in appearance. In four patients the infiltrate was dominated by large cells. In the remaining patients the reactive infiltrate defined the dominant cell population. The neoplastic cells expressed CD20, CD30, CD43, and BCL-2. In two cases associated with methotrexate therapy, Epstein-Barr virus expression was observed amid the neoplastic cell populace. CONCLUSIONS: CD30+ PCBCL is a distinctive form of B-cell lymphoma presenting in elderly patients and can be associated with a very good prognosis. In some patients the intensity of reactive inflammation obscures the diagnosis. In the authors' experience almost a third of the cases were associated with Epstein-Barr virus infection and methotrexate therapy, suggesting a distinctive association.     

Detection of HTLV-I proviral sequences in CD30-positive large cell cutaneous T-cell lymphomas.

To investigate the possibility that cutaneous T-cell lymphomas of large cell type may be associated with human T-cell leukemia/lymphoma virus type I infection in nonendemic regions, tissue samples from six cases of large cell cutaneous T-cell lymphoma and four cases of small cell cutaneous T-cell lymphoma were screened for the presence of integrated proviral human T-cell leukemia/lymphoma virus type I DNA. Combined use of Southern blot hybridization and enzymatic DNA amplification revealed human T-cell leukemia/lymphoma virus type I-specific sequences in all cases of large cell cutaneous T-cell lymphoma and in none of the cases of small cell cutaneous T-cell lymphoma. These results suggest that in nonendemic areas, a significant proportion of large cell cutaneous T-cell lymphoma cases are associated with human T-cell leukemia/lymphoma virus type I.     

Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive, large-cell anaplastic lymphomas using the polymerase chain reaction.

Ki-1 (CD30)-positive, large-cell anaplastic lymphoma (LCAL) is a distinctive subset of non-Hodgkin's lymphoma; morphologically, the neoplastic cells of LCAL may closely resemble Reed-Sternberg cell variants of Hodgkin's disease. The neoplastic cells in Hodgkin's disease are often CD30-positive, as are some of the transformed lymphocytes in infectious mononucleosis. Recent evidence suggests an etiologic role for the Epstein-Barr virus (EBV) in Hodgkin's disease. Because of the phenotypic similarities between Hodgkin's disease and LCAL, we used the polymerase chain reaction (PCR) to analyze eight specimens of LCAL for EBV genome. Diagnoses were established by paraffin section morphology and immunohistochemistry. For comparison, we also analyzed nine non-Hodgkin's lymphomas other than the LCAL type, three Hodgkin's disease specimens, and nine non-neoplastic lymph nodes. PCR was performed using DNA extracted from frozen tissue; DNA was amplified using two sets of oligonucleotide primers corresponding to the BamH1 W-fragment of the EBV genome. Amplified EBV genome was obtained from all specimens except for one mantle zone lymphoma, one diffuse mixed-cell lymphoma, and six non-neoplastic lymph nodes. EBV terminus region probing and in situ hybridization techniques, each less sensitive than PCR, were performed in selected cases in an attempt to corroborate our PCR results. Only 2 of 13 specimens contained EBV detectable by these other techniques, and neither specimen was a LCAL. In view of the high incidence of latent EBV infections in humans, the biologic significance of our PCR results is uncertain. Despite the detection of EBV genome by PCR in a high percentage of lymphomas, we were unable to substantiate an etiologic role for EBV in LCAL. The PCR technique may be too sensitive to provide meaningful data on the possible role of EBV in lymphomagenesis.     

Secondary pleural involvement by an AIDS-related anaplastic large cell (CD30+) lymphoma simulating metastatic adenocarcinoma

We report a patient with acquired immunodeficiency syndrome with secondary pleural and pulmonary involvement by a CD30+ anaplastic large cell lymphoma (ALCL) that morphologically simulated metastatic adenocarcinoma. We describe the morphologic findings in order to heighten awareness that CD30+ ALCL may mimic metastatic adenocarcinoma in a body fluid or bronchial brushing and should be considered in the differential diagnosis. Primary body cavity based (PCBC) AIDS-related lymphoma is a relatively newly described disease entity with morphologic features bridging ALCL and large cell immunoblastic lymphoma with a CD30+ null immunophenotype. A morphology mimicking adenocarcinoma has not been previously described in this entity but should be considered in a patient with AIDS presenting exclusively with a serous effusion. Appropriate immunoperoxidase staining should aid in these differential diagnoses. Diagn. Cytopathol. 1998;18:113–117. © 1998 Wiley-Liss, Inc.     

Hodgkin's disease and CD30-positive anaplastic large cell lymphomas--a continuous spectrum of malignant disorders. A quantitative morphometric and immunohistologic study.

The authors have examined cellular areas of lymphoma tissue in 28 cases of Hodgkin's disease (HD) or anaplastic large cell lymphoma (ALCL, 'Ki-1 cell lymphoma') to evaluate the boundaries between the two entities. Methods applied included conventional histology; test point analysis; semiautomated morphometry of nuclear profile features of Reed-Sternberg and other atypical large cells (RSALCs); and immunohistochemistry of these elements on all paraffin sections and, in 15 cases, on frozen sections. Mean nuclear profile morphotypes of RSALCs per case varied independently of immunophenotype and histologic diagnosis. Conversely, immunohistochemistry demonstrated significant, although not consistent, preferential positivities of these CD30+ elements for CD15 in HD, and for epithelial membrane antigen (EMA) and CD43 in ALCLs. In the latter, RSALCs also exhibited a tendency for CD45 and CD45RO positivity and for the expression of T-cell-associated antigens. However, there were considerable overlaps. This continuous spectrum of RSALC nuclear profile morphotypes and immunophenotypes, ranging from HD over questionable cases, intermediate between HD and ALCL, to ALCLs, was paralleled by differences in the reactive component of lymphomas. Lymphocytes and granulocytes were significantly deficient in ALCLs.     

Primary CD30/Ki-1 positive anaplastic large cell lymphoma of skeletal muscle with der(17)t(1;17)(q11;p11)

CD30/Ki-1 positive anaplastic large cell lymphoma (Ki-1 ALCL) frequently exhibits extranodal disease and chromosomal t(2;5)(p23;q35). An 11-year-old girl presented with an intramuscular tumor of the right upper arm. Tumors of the chest wall, left arm and leg, hepatomegaly, pleural effusion, and enlarged lymph nodes then developed. The intramuscular tumor and pleural effusion showed a diffuse infiltration of large atypical cells with abundant amphophilic cytoplasms. The tumor cells were positive for CD30, CD2, CD45RO, and p80, but were negative for other T-cell, B-cell, and myeloid cell antigens. She was diagnosed as having Ki-1 ALCL with a T-cell origin. Cytogenetic studies showed an abnormal karyotype including a der(17)t(1;17)(q11;p11). She received seven cycles of intensive chemotherapy followed by an autologous peripheral blood stem cell transplantation, and has been in complete remission for more than two years. The primary involvement of skeletal muscle is quite uncommon in ALCL, and an abnormal karyotype including t(1;17)(q11;p11) has not been reported previously. Since a high frequency of aberrations of 1p36/1q12 or 17p13.3 was detected in sarcoma cells, the presence of suppressor genes is suggestive in these sites.     

Primary gastric Ki-1 positive anaplastic large cell lymphoma: A report of two cases

Two cases with primary gastric Ki-1 positive anaplastic large cell lymphoma are presented. Morphologic features of both cases involved pleomorphism of the neoplastic cells, fibrosis and lymphatic infiltration. The neoplastic cells in both cases were positive for BerH₂ (CD30), LCA(CD45), lysozyme and alpha-1-antitrypsin (α₁-AT). In additional case, the neoplastic cells were additionally positive for MAC387 and (α₁,-antichymotrypsin (α,-ACT). The neoplastic cells in these cases were negative for L26(CD20), UCHL-1 (CD45RO), DAKO CD3 and epithelial membrane antigen (EMA). According to the results of the phenotypic studies, the authors consider that the neoplastic cells have some of the features of histiocytes.
Both patients at 2 and 8 years after surgery without chemotherapy are disease free. This lymphoma is well known to be frequently misdiagnosed as undifferentiated carcinoma. Although rare in occurrence, recognition of this primary lymphoma in the stomach has a significant clinical implication, as the authors consider that its prognosis might be better than undifferentiated carcinoma of the stomach.     

结肠原发性CD3O阳性间变性大细胞淋巴瘤1例报道及文献复习

目的 探讨结肠原发问变性大细胞淋巴瘤(ALCL)的组织学特点及免疫组化特征。方法 运用组织形态学、免疫组化方法研究1例发生在结肠的间变性大细胞淋巴瘤并结合文献进行讨论。结果 间变性大细胞淋巴瘤其形态学表现为多样性，免疫组化显示CD30 ，另外CD45、CD45RO、CD3和EMA也可 。结论 间变性大细胞淋巴瘤发生在结肠非常罕见，其形态学和免疫组化表型有一定的特殊性，并且预后良好，有必要与其它类型淋巴瘤、霍奇金淋巴瘤、恶性组织细胞增生症、恶性黑色素瘤、低分化腺癌等进行鉴别。